During vertebrate gastrulation, massive cell movements shape the basic body plan. Key components of gastrulation are convergence and extension (C&E) movements, which narrow and lengthen the embryonic tissues, respectively. By studying knypek;trilobite non-canonical Wnt mutants with impaired C&E, I demonstrate crucial roles of C&E gastrulation movements in multiple aspects of zebrafish somite development. Combining time-lapse analyses and computational simulations, I show that C&E movements of the medial presomitic mesoderm are achieved by the cooperation of planar and radial cell intercalations that preferentially separate anterior and posterior neighbors. In knypek;trilobite double mutants, the anteroposterior bias of cell intercalations is reduced and the asymmetric localization of non-canonical Wnt components is lost, revealing that non-canonical Wnt signaling defines distinct properties of anterior and posterior cell edges to bias the orientation of cell intercalation. Using cell tracing analyses and genetic manipulations, I demonstrate that C&E mediates the specification and fate maintenance of slow muscle precursors, the adaxial cells. During gastrulation, C&E regulates the number of specified adaxial cells by defining the size of the interface between the inducing axial and target presomitic tissues. After somite forms, convergence movements ensure the tight apposition of adaxial cells to the notochord, which is necessary for their continuous Hedgehog reception and fate maintenance. I further demonstrate that in knypek;trilobite double mutants, impaired C&E disrupts notochord development, which in turn impedes the adaxial cell shape changes and interferes with their lateral migration during later somitogenesis. <p>
Additionally, in a genetic screen for genes essential for zebrafish early development, we isolated the calamityvu69 mutation that affects pigmentation and notochord development. We determined that calamityvu69 inactivates a zebrafish homolog of the human Menkes atp7a gene, which is critical for copper homeostasis in humans. Genetic mosaic analyses indicate that atp7a acts cell-autonomously in melanocytes to ensure melanin synthesis. Identification of the calamityvu69 mutant establishes a novel vertebrate model for studying the human Menkes disease and copper metabolism. <p>
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02152007-100239 |
| Date | 27 February 2007 |
| Creators | Yin, Chunyue |
| Contributors | Todd R. Graham, Lilianna Solnica-Krezel, Bruce Appel, Christopher V.E. Wright, Chin Chiang |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02152007-100239/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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